rs188233779

Variant names:

• chr16-1834371-G-A
• rs188233779
• NM_001163560.3:c.1306-5C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-1834371-G-A
• chr16-1834371-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001163560.3(MEIOB):​c.1306-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0047 in 1,484,288 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0048 (26 hom.)
• Consequence: MEIOB NM_001163560.3 splice_region, intron
• Scores: Splicing: ADA: 0.00006780
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.801
• Publications: 2 publications found

Genes affected

MEIOB (HGNC:28569): (meiosis specific with OB-fold) Predicted to enable chromatin binding activity; single-stranded DNA 3'-5' exodeoxyribonuclease activity; and single-stranded DNA binding activity. Predicted to be involved in double-strand break repair via homologous recombination; fertilization; and meiotic nuclear division. Predicted to be located in cytoplasm. Implicated in spermatogenic failure 22. [provided by Alliance of Genome Resources, Apr 2022]

FAHD1 (HGNC:14169): (fumarylacetoacetate hydrolase domain containing 1) Enables acetylpyruvate hydrolase activity; fumarylpyruvate hydrolase activity; and oxaloacetate decarboxylase activity. Located in cytosol; mitochondrion; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-1834371-G-A is Benign according to our data. Variant chr16-1834371-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 715773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00355 (539/152042) while in subpopulation NFE AF = 0.00519 (353/68020). AF 95% confidence interval is 0.00474. There are 4 homozygotes in GnomAd4. There are 245 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163560.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEIOB	NM_001163560.3	MANE Select	c.1306-5C>T		splice_region intron	N/A	NP_001157032.1	Q8N635-2
	MEIOB	NM_152764.3		c.1219-5C>T		splice_region intron	N/A	NP_689977.2	Q8N635-1
	FAHD1	NM_001018104.3		c.628-3645G>A		intron	N/A	NP_001018114.2	Q6P587-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEIOB	ENST00000325962.9	TSL:5 MANE Select	c.1306-5C>T		splice_region intron	N/A	ENSP00000314484.3	Q8N635-2
	FAHD1	ENST00000382668.8	TSL:1	c.628-4891G>A		intron	N/A	ENSP00000372114.5	Q6P587-2
	MEIOB	ENST00000397344.7	TSL:5	c.1219-5C>T		splice_region intron	N/A	ENSP00000380504.3	Q8N635-1

Frequencies

GnomAD3 genomes AF: 0.00355 AC: 539 AN: 151924 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.00102

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00519

Gnomad OTH AF: 0.00575

GnomAD2 exomes AF: 0.00366 AC: 854 AN: 233352 AF XY: 0.00368

Gnomad AFR exome AF: 0.000877

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.00766

Gnomad EAS exome AF: 0.0000569

Gnomad FIN exome AF: 0.00178

Gnomad NFE exome AF: 0.00492

Gnomad OTH exome AF: 0.00667

GnomAD4 exome AF: 0.00483 AC: 6434 AN: 1332246 Hom.: 26 Cov.: 20 AF XY: 0.00488 AC XY: 3264 AN XY: 668354

African (AFR) AF: 0.000528 AC: 16 AN: 30328

American (AMR) AF: 0.00184 AC: 73 AN: 39740

Ashkenazi Jewish (ASJ) AF: 0.00809 AC: 200 AN: 24728

East Asian (EAS) AF: 0.00 AC: 0 AN: 38910

South Asian (SAS) AF: 0.00542 AC: 431 AN: 79536

European-Finnish (FIN) AF: 0.00231 AC: 123 AN: 53202

Middle Eastern (MID) AF: 0.00437 AC: 24 AN: 5496

European-Non Finnish (NFE) AF: 0.00524 AC: 5263 AN: 1004260

Other (OTH) AF: 0.00542 AC: 304 AN: 56046

GnomAD4 genome AF: 0.00355 AC: 539 AN: 152042 Hom.: 4 Cov.: 31 AF XY: 0.00330 AC XY: 245 AN XY: 74338

African (AFR) AF: 0.00102 AC: 42 AN: 41338

American (AMR) AF: 0.00465 AC: 71 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00435 AC: 21 AN: 4824

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00519 AC: 353 AN: 68020

Other (OTH) AF: 0.00569 AC: 12 AN: 2108

Alfa AF: 0.00401 Hom.: 1

Bravo AF: 0.00348

Asia WGS AF: 0.00173 AC: 7 AN: 3478

EpiCase AF: 0.00465

EpiControl AF: 0.00512

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.59
PhyloP100		0.80
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000068
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs188233779; hg19: chr16-1884372;